The ultraviolet inactivation of enzymes is being investigated with flash photolysis techniques, with emphasis on identifying the initial photochemical intermediates and their relationship to final products and activity loss. The previous work will be extended to carboxypeptidase A to study the influence of the liganded zinc atom on the reactions of photoelectrons ejected from aromatic residues. This work will be augmented with studies on Bence-Jones protein, where independent luminescence studies indicate intramolecular electron transfer between aromatic residues and a disulfide bridge. The investigation of 8-methoxypsoralen photochemistry will be continued and extended to other psoralen derivatives of interest in connection with photochemotherapy of psoriasis. This part of the program includes flash photolysis studies of psoralens in the presence of nucleic acid substrates, studies of photosensitized inactivation of enzymes emphasizing the generation of singlet oxygen by psoralen sensitizers, and fluorescence lifetime measurements of psoralens in the presence of binding polynucleotide substrates. The detailed investigations of protein reactions are relevent to recent work on cellular damage where the primary photochemical targets cannot be identified with chromosomal DNA. The psoralen work is directed towards understanding the initial stages of psoralen reactions with DNA, particularly the effect of dark binding interactions on the relative efficiency of Type I (drug-substrate) and Type II (drug-oxygen) pathways. BIBLIOGRAPHIC REFERENCES: Flash Photolysis of Enzymes, L.I. Grossweiner, A.G. Kaluskar and J.F. Baugher, International Journal of Radiation Biology, 29, 1-16 (1976). Decay Kinetics of the Photochemical Hydrated Electron, L.I. Grossweiner and J.F. Baugher, Journal of Physical Chemistry, 81, (1977).